The invention generally relates to stem cells and therapeutic uses thereof. More particularly, the invention relates to transgenic stem cells that have been genetically modified with an exogenous polynucleotide. The use of transgenic stem cells for the treatment of medical conditions defined by an ischemic penumbra are within the scope of the invention.
In pathology and anatomy the penumbra is the area surrounding an ischemic event such as an ischemic, thrombotic or embolic stroke. Immediately following the event, blood flow and therefore oxygen transport is reduced locally, leading to hypoxia of the cells near the location of the original insult. This can lead to cell death and amplify the original damage from the infarction, however, the penumbra area may remain viable after an ischemic event due to the collateral arteries that supply the penumbral zone.
As time elapses after the onset of stroke, the extent of the penumbra tends to decrease (British Medical Bulletin, 65 (1), 145-157). Without relying on any scientific principal or theory, the existence of a penumbra implies that salvage of the cells is possible. There is a high correlation between the extent of spontaneous neurological recovery and the volume of penumbra that escapes infarction; therefore, saving and restoring the function the penumbra should improve the clinical outcome.
One widely accepted definition for penumbra describes the area as “ischemic tissue potentially destined for infarction but not yet irreversibly injured and the target of acute therapies” (Stroke 32: 2657). The original definition of the penumbra referred to areas of the brain that were damaged but not yet dead, and offered promise to rescue the brain tissue with the appropriate therapies (Nature Medicine 14 (5): 497-500).
What is needed in the art therefore is a method and composition for rescuing the ischemic penumbra thereby providing enhanced tissue regeneration and recovery outcomes for a variety of ischemic conditions, including, but not limited to stroke, myocardial infarction, retinal ischemia, pancreatic ischemia and ALS.